Acute Respiratory Distress Syndrome (ARDS)
Conditions
Keywords
acute respiratory distress syndrome, subphenotypes, ADRS
Brief summary
About 10% of patients admitted to the ICU suffer from ARDS, with a mortality rate of around 35-45%. The lack of therapeutic innovation in ARDS can be partly explained by the heterogeneity of patients included under this definition. A better understanding of the pathophysiological mechanisms underlying the different patient phenotypes is essential to develop new therapeutic strategies. Objectives: To characterize the inflammatory profile of patients with ARDS using circulating biomarkers and single-cell RNA sequencing of pulmonary immune cells. The investigators hypothesize that there is a correlation between the profile of serum biomarkers (inflammatory sub-phenotypes), the transcriptome of pulmonary immune cells. Briefly the experimental scheme is as follow: * Population: patients with ARDS under invasive mechanical ventilation in the ICU. * Intervention: 1. Determination of the inflammatory subphenotype on circulatory inflammatory biomarkers. 2. Characterization of inflammation by single cell RNA sequencing on lung immune cells collected on broncho-alveolar fluid.
Detailed description
Acute Respiratory Distress Syndrome (ARDS) is the most severe form of pulmonary failure. It is defined by bilateral radiologic opacities associated with severe hypoxemia, confirmed by a PaO₂/FiO₂ ratio \<300 in the absence of a cardiac cause. About 10% of patients admitted to the Intensive Care Units (ICU) develop ARDS, and this diagnosis is associated with an in-hospital mortality of 35-45%. Like sepsis, ARDS leads to long-term complications. It is associated with physical deconditioning and reduced quality of life that can persist up to five years after the episode. Survivors are readmitted to the ICU within a year in 30% of cases. Moreover, excess mortality among ARDS survivors is attributable, in nearly one-third of cases, to a new acute respiratory infection. The lack of therapeutic advances in ARDS has led researchers to better characterize patients with this condition. Different subphenotypes have been identified based on plasma inflammatory biomarker profiles, which are associated with distinct responses to treatments (such as corticosteroids, ventilatory management, and fluid management) and variable prognoses. The mechanisms underlying these different biological subphenotypes remain unknown. To further explore this concept, it is necessary to precisely identify subpopulations of patients who present with similar clinical features but distinct biological phenotypes driven by unique pathophysiological mechanisms. Establishing these different ARDS endotypes is essential for the development of innovative and targeted therapeutic strategies. Our hypothesis is that the different biological subphenotypes of ARDS reflect distinct profiles of pulmonary immune cell populations, representing a first step toward understanding ARDS endotypes. Identifying these endotypes is a crucial step for developing targeted and innovative therapeutic strategies aimed at reducing ARDS-related morbidity and mortality. This is the objective of the proposed project.
Interventions
None listed
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ARDS risk factors: bacterial or viral pneumonia, extrapulmonary infection, major trauma, transfusion, inhalation injury, or shock. * Pulmonary edema not explained by a cardiogenic cause or volume overload. * Onset of respiratory symptoms within \<7 days. * Bilateral pulmonary involvement on chest X-ray, CT scan, or ultrasound. * PaO₂/FiO₂ ≤ 300 assessed with PEEP ≥ 5 cmH₂O.
Exclusion criteria
* ARDS with intubation for more than 48 hours. * Contraindications to bronchoscopy: effective anticoagulation, dual antiplatelet therapy, thrombocytopenia \<50 G/L. * Pre-existing immunodeficiency: active solid tumor or remission \<5 years, active hematologic malignancy or remission \<5 years, systemic disease (even without specific treatment), solid organ or bone marrow transplant, HIV infection with CD4 \<200/mm³. * Cardiac arrest with a poor prognosis (NSE \>60, malignant EEG, diffuse ischemia on imaging, loss of trunk reflexes). * Patients \<18 year-old * Patients under legal guardianship, curatorship, or deprived of liberty. * Ongoing pregnancy. * Patients without social security coverage.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Single cell RNA sequencing of pulmonary immune cells | At baseline | Single cell RNA sequencing of pulmonary immune cells collected during a bronchoalveolar lavage at inclusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | At day 90 | Mortality rate at day 90 |
| Time without respiratory support | At day 28 | Number of days alive without mechanical ventilation on day 28 after inclusion or on discharge from intensive care if this occurs before the 28th day |
| Length of stay in intensive care | From inclusion to ICU discharge up to 1 year | Number of days in intensive care. |
| Number of secondary infections | At day 90 | Rate of secondary infections defined as a new prescription of antibiotics |
| Impact perceived on quality of life | At day 90 | Quality of life assessed though the SF-12 questionnaire on the phone. |
| Dsypnea scale | At day 90 | Dyspnea scale assessed through mMRC questionnaire on the phone |
| Organ failure | At baseline | SOFA score assessment |
| Need for vasopressor | At baseline | Need for vasopressor (epinephrine or norepinephrine) |
| Vasopressor free days | At day 28 or at discharge from intensive care | Number of days alive without vasopressors on day 28 after inclusion or on discharge from intensive care if this occurs before the 28th day. |
Countries
France
Contacts
CONTACTPierre-Louis BLOT, MD
CONTACTBenjamin Chousterman, MD PhD
Outcome results
None listed